Ferrocenyl–triazole complexes and their use in heavy metal cation sensing

Complexes tris((1-ferrocenyl-1H-1,2,3-triazol-4-yl)methyl)amine (3), bis((1-ferrocenyl-1H-1,2,3-triazol-4-yl)methyl)amine (6), bis((1-ferrocenyl-1H-1,2,3-triazol-4-yl)methyl)ether (7), and 1-ferrocenyl-1H-1,2,3-triazol-4-yl)methanamine (9) were synthesized using the copper-catalyzed click reaction. Complexes 3, 6, 7, and 9 were characterized using NMR (1H and 13{1H}) and IR spectroscopy, elemental analysis, and mass spectrometry. Structures of 3, 7, and 9 in the solid state were determined using single-crystal X-ray diffraction. It was found that the triazole rings were planar and slightly twisted with respect to the cyclopentadienyl groups attached to them. Chains and 3D network structures were observed due to the presence of π⋯π and C–H⋯N interactions between the cyclopentadienyl and triazole ligands. A reversible redox behavior of the Fc groups between 239 and 257 mV with multicycle stability was characteristic for all the compounds, revealing that the electrochemically generated species Fc+ remained soluble in dichloromethane. Electrochemical sensor tests demonstrated the applicability of all the complexes to enhance the quantification sensing behavior of the screen-printed carbon electrode (SPCE) toward Cd2+, Pb2+, and Cu2+ ions.


Introduction
0][11] The detection of such metals, for example, using state-of-the-art techniques, including atomic-uorescence and inductively coupled plasma mass spectrometry, is expensive and requires high operating costs (e.g., for sample preparation, training operators, time). 12,13ecently, chemo-sensing portable devices with advantages of simple, rapid, sensitive, and selective operation are still lacking.][42][43][44][45][46][47][48] Herein, we present the synthesis and characterization of diverse ferrocenyl-containing triazole complexes.In addition, their structural and electrochemical properties are reported.Their use as modier materials to design a voltammetric sensor for the quantication of heavy metals is discussed.

General data
All the reactions were carried out under an argon atmosphere (5.0) employing standard Schlenk techniques.Tetrahydrofuran and N,N-dimethylformamide were puried by distillation from sodium/benzophenone and calcium hydride, respectively.For the electrochemistry experiments, HPLC grade dichloromethane was puried by distillation from calcium hydride.For the column chromatography, alumina with a particle size of 90 mm (Standard, Merck KGaA) and silica with a particle size of 40-60 mm (230-400 mesh (ASTM), Fa.Macherey-Nagel) were used.

Instruments
A Bruker Avance III 500 spectrometer operating in the Fourier transform mode at 298 K was utilized to acquire the NMR spectra, including ( 1 H NMR (500.3MHz) and 13 C{ 1 H} NMR (125.8MHz)).Chemical shis (d) are reported in parts per million (ppm) relative to tetramethylsilane using the solvent as the internal reference (CDCl 3 : 1 H NMR d = 7.26 ppm; 13 C{ 1 H} NMR d = 77.16ppm). 49A FT-Nicolet IR 200 spectrometer was employed to capture the infrared spectra.The determination of the melting points utilized analytical pure samples tested with a Gallenkamp MFB 595 010 M melting point apparatus.
Elemental analyses were conducted using a Thermo FlashEA 1112 Series instrument, and high-resolution mass spectra were recorded using a micrOTOF QII Bruker Daltonite spectrometer.

Electrochemistry
Electrochemical measurements were performed using 1.0 mmol L −1 solutions of the analytes and [N n Bu 4 ][B(C 6 F 5 ) 4 ] as the supporting electrolyte in anhydrous dichloromethane at 25 °C. 32,33,38,54he instrumentation consisted of a Radiometer Gamry interface 1010E workstation interfaced with a personal computer.The measurement cell comprised three electrodes: a Pt auxiliary electrode, a glassy carbon working electrode, and a Ag/Ag + (0.01 mol L −1 AgNO 3 ) reference electrode.The working electrode underwent pretreatment involving polishing on a Buehler microcloth subsequently with 1 mm and 1/4 mm diamond paste.The reference electrode composed a silver wire, which was inserted into a Luggin capillary with a Vycor tip lled with a solution of 0.01 mol L −1 [AgNO 3 ] and 0.1 mol L −1 [N n Bu 4 ] [B(C 6 F 5 ) 4 ] in acetonitrile.This Luggin capillary was further inserted into a second Luggin capillary with a Vycor tip lled with a solution of 0. [54][55][56][57][58][59][60] Under these conditions, all the experiments demonstrated that all the oxidation and reduction processes were reproducible in the range of ±5 mV.The experimental potentials were internally referenced against a Ag/Ag + reference electrode, while all the presented results are referenced against ferrocene (as internal standard) as recommended by IUPAC. 61The experimentally measured potential was adjusted into E vs. FcH/FcH + by adding −614 mV.This correction was applied when decamethylferrocene served as an internal standard.3][64] A Microso Excel worksheet was employed to process the data, ensuring the formal redox potentials of the FcH/FcH + couple were set to E°= 0.0 V. 62 The cyclic voltammograms were obtained aer two scans and were deemed to be steady-state cyclic voltammograms, wherein the signal pattern remained consistent with the initial sweep.

Electrochemical sensing
The sensing measurements were conducted with a PalmSens4 portable potentiostat (Palmsens BV, GA Houten, Netherlands) and screen-printed carbon electrodes (SPCEs) featuring a carbon counter electrode, a graphite working electrode, and a Ag/AgCl reference electrode. 65The selection of an appropriate buffer as an electrolyte for metal analysis was necessary to avoid the metal cations precipitation. 66Therefore, HAcO-NaAcO buffer solution (ABS (0.1 M), pH = 5.6) was used as the supporting electrolyte.The electrochemical responses for ABS (0.1 M, pH = 5.6) containing the target cations were recorded by square wave voltammetry measurements in the potential range from -1.3 V to + 1.0 V, modulation amplitude of 50 mV, step potential of ±5 mV, and equilibration time of 5 s.

Functionalization of the SPCEs with the ferrocenyltriazole complexes
8][69] Thus, dichloromethane solutions (1.0 mM) of the ferrocenyl-triazole complexes 3, 6, 7, and 9 were prepared and used to modify the working SPCEs using the drop-casting technique with the desired complex solution (1 mL × 5 times) and then dried at room temperature and atmospheric pressure for approximately 6 h.

Single-crystal X-ray diffraction analysis
The diffusion of pentane into a dichloromethane solution containing 3, 7, or 9 at ambient temperature offered suitable single crystals for X-ray diffraction analysis.An Oxford Gemini S diffractometer (3, Mo Ka radiation, l = 0.71073 Å, 120 K) and a Bruker Venture D8 diffractometer (7/9, Cu Ka radiation, l = 1.54178Å, 100 K) were utilized to acquire the corresponding data.The molecular structures were determined through direct methods and rened using full-matrix least-squares procedures on F o 2 using SHELXS-and SHELXL-2013 implemented in the WINGX v2013.3suite. 70,71All non-hydrogen atoms were rened anisotropically, and a riding model was employed for treatment of the hydrogen atom positions.
In the case of 7, the data set was treated with the command SQUEEZE of the PLATON program. 72Within the unit cell (V = 2650.4(2)Å 3 ), a volume of solvent-accessible voids of 476.1 Å 3 (ca.18%) and an electron count per unit cell of 192.4 were determined.Considering that one dichloromethane packing solvent molecule possessed 42 electrons, the calculated total electron count per unit cell (Z = 4, Cc) was 168 electrons, in agreement with the SQUEEZE calculated value.Each dichloromethane packing solvent involved the next three non-hydrogen atoms, summing up to 12 non-hydrogen atoms in the VOIDs.As it is reasonable to assume a volume per non-hydrogen atom of disordered solvents in VOIDS of 40 Å 3 , an overall VOID volume of 480 Å 3 was calculated.This is in excellent agreement with the SQUEEZE calculated value of 476.1 Å 3 .

Synthesis
In accordance with the classical click chemistry protocol, 1azidoferrocene (1), which is accessible by the reaction of 1-bromoferrocene with sodium azide in the presence of copper(I) bromide, 52,74 was reacted with 3.3 equiv. of tripropargylamine in a tetrahydrofuran-water mixture in the ratio of 6 : 1 (v/v) accompanied by the addition of an aqueous solutions of CuSO 4 and Na-ascorbate at 25 °C for 48 h.6][77][78][79][80][81] However, when using this classical click synthesis protocol for the preparation of 6 and 7 only very low yields could be obtained, while the synthesis of 9 was unsuccessful.Hence, complex 3 was used as an alternative stabilizing ligand instead of tris-(benzyltriazolylmethyl)amine (TBTA) for in situ generation of the respective Cu(I) catalyst. 78Thus, when 1 was reacted with 2.2 equiv. of dipropargylamine or dipropargyl ether and 1.1 equiv. of propargylamine, then 6, 7, and 9 could be isolated in 88-92% yields (Experimental section, Scheme 1).

Characterization
Compounds 3, 6, 7, and 9 were obtained as air-stable yellowbrownish solid materials at room temperature.They were characterized by IR, and NMR spectroscopy ( 1 H, 13   Paper RSC Advances and 9 in the solid state were determined by single-crystal X-ray diffraction analysis.The presence of the amine functionality in 9 and 6 could be conrmed by IR spectroscopy by intense N-H stretching and bending vibrations at 3138 and 1206 cm −1 (9) or 3138 and 1106 cm −1 (6).New bands at 1107 cm −1 with a moderate intensity grew which were characteristic of n CN vibrations in 3, 6, and 7.In addition, stretching vibrations (1218 cm −1 (3), 1220 cm −1 (6), 1222 cm −1 (7), and 1213 cm −1 (9)) typical for aromatic amines conrmed the successful introduction of a triazole functionality.Within 7, the ether functionality was characterized by a C-O stretching vibration at 1042 cm −1 .
In the 1 H NMR spectra of 3, 6, 7, and 9, the Fc units showed the expected pattern between 4.2-4.9ppm (Experimental).While the C 5 H 5 protons resonated as a singlet at 4.2 ppm, and the C 5 H 4 a and b protons appeared as pseudo-triplets at 4.3 and 4.8 ppm with J HH = 2.0 Hz.The triazole-heterocyclic units showed singlets at 8.09 ppm (3), 7.87 ppm (6), 7.85 ppm (7), and 7.69 ppm (9).The CH 2 protons could be detected as singlets at 3.87 ppm (3), 4.02 ppm (6), 4.27 ppm (7), and 4.04 ppm (9).The protons of the amine functionality in 6 and 9 were found as singlets at 2.04 and 1.57 ppm.Within the 13 C NMR spectra, all the complexes showed individual signals for the triazole moieties at ca. 145 and 122 ppm, as well as for the ferrocenyl moieties between 62 and 94 ppm in the spectral region.][84] Single crystals of 3, 7, and 9 suitable for X-ray diffraction analysis were obtained by the diffusion of pentane into a dichloromethane solution containing either 3, 7, or 9 at ambient temperature.The crystal and structure renement data are presented in Table 1.The molecular structures of 3, 7, and 9 with the atom labeling scheme are provided in Fig. 1-3.The bond distances (Å) and valence and torsion angles (deg) are given in Table S1 (see the ESI †).
All the other structural parameters were unexceptional and compared well with those of related species. 86,87On the other hand, in the solid state, C-H/N interactions occur between the 1H-1,2,3-triazole rings, leading to the formation of chains along the a-axis, as illustrated in Fig. S1 (see the ESI †).Within the solid-state analysis of compound 3, there were paralleldisplaced p/p interactions noted between two cyclopentadienyl rings, resulting in the formation of threedimensional chains along the c-axis (Fig. S2, see the ESI †).
Compound 9 crystallizes in the monoclinic space group C2/c.The structure of 9 is presented in Fig. 3, which shows that 9 crystallizes in the form of [( 9) 2 × H 2 O].Thereby, the two crystallographically different molecules of 9 are denoted as A (including Fe1) and B (including Fe2) and within the asymmetric unit, one water molecule is present.In both molecules, the two cyclopentadienyl rings exhibit a tilt angle of 0.9(4)°/ 0.8(9)°, and they are approximately eclipsed with a twist angle of −1.1( 8)°(N1-C6-Fe1-C1)/4.8( 7)°(N5-C26-Fe2-C21) for the A and B molecules, respectively.The remaining geometrical parameters within the ferrocenyl framework are typical. 90As anticipated, the 1H-1,2,3-triazole ring is planar, and it exhibits a slight twist concerning the attached cyclopentadienyl groups, resulting in dihedral angles of 10.8(3)°and 6.8(8)°forA and B, respectively.The most signicant difference between the two molecules comprising the asymmetric unit is evident in the dihedral angle between the methanamine and the 1H-1,2,3-triazole unit, measuring 7.3°for molecule A, in contrast to 73.1°f or molecule B. Interestingly, the water molecule exists within the crystal packing connecting both molecules through hydrogen bonding between the NH 2 groups and the H 2 O. Furthermore, a water molecule forms a hydrogen bond with the 1H-1,2,3-triazole ring of molecule B.
Through involving the Fc rings, C-H/p interactions between molecules A and B lead to the formation of a chain.Further interactions via C-H/p between Fc rings and 1,2,3triazole rings lead to the formation of a 2D structure (Fig. S5 and S6, see the ESI †).In the perpendicular direction, further C-H/ p interactions between Fc and 1H-1,2,3-triazole rings and C-H/p interactions between Fc rings beside C-H/N, CH 2 /C, N/N contacts and p/p stacking furnish the 3D structure (Fig. S7, see the ESI †).

Hirshfeld surfaces analysis
Further analysis of the molecular packing scheme was performed by calculating the Hirshfeld surfaces and two-dimensional ngerprint plots (overall and decomposed) employing Crystal Explorer 17 (ref.93) using standard protocols 94 to discern and clarify the impact of the noteworthy intermolecular interactions observed in the crystal packing, which were consistent across the three compounds, prompting an examination of the role played by weak non-covalent interactions in the supramolecular assembly.][97][98][99][100]  For each compound, in the crystal packing the bright and deep-red spot in the Hirshfeld surface indicates the closest distance between the atoms at the exterior (d e ) and interior (d i ) of the compound.Fingerprint plots (Fig. S8-S10, refer to the ESI †) illustrate that H/H interactions predominantly govern the surface contacts, which aligns with expectations given the abundance of H atoms in the molecule.Additionally, H/C/C/ H and H/N/N/H contacts also play notable roles in the surface interactions (Table S2, see the ESI †).
Fig. 4a displays the Hirshfeld surfaces of 3. The prominent red areas on the Hirshfeld surfaces represent classical H/N/ N/H hydrogen bonds, while the less pronounced red circles denote weaker p/p stacking contacts.In the d norm map of 7, the dark red regions are associated with N/H/N/H hydrogen bonds and p/p stacking interactions, while the bright-red regions are attributed to C-H/p interactions (Fig. 4b).Hydrogen bonding interaction between 9 and the co-crystallized water molecule in the crystal structure was observed in the Hirshfeld surfaces.Fig. 4c represents the Hirshfeld surface of 9.As expected, deep-red spots were observed corresponding to the presence of hydrogen bonds (H/O/O/H, H/N/N/H), while the bright-red spots corresponded to the presence of C-H/p stacking.

Electrochemistry
,101 The electrochemical measurements were conducted at 25 °C under an argon atmosphere and referenced against the potential of the FcH/FcH + redox couple.In all compounds, reversible and well-dened redox events were observed, as illustrated in Fig. 5.The electrochemical data are consolidated in Table 1.The multicyclic experiments indicated the stability of the Fc/Fc + redox couples for all the compounds.
To validate the potential of the ferrocenyl-triazole materials more comprehensively for detecting multiple heavy metal ions simultaneously, we recorded their SWV responses with different concentrations (0-1000 mM) of Cd 2+ , Pb 2+ , and Cu 2+ (Fig. 9, Table 3).It was noteworthy that the observed non-linearity and splitting in the calibration curve (Fig. 9) could be attributed to the interaction between heavy metal ions and the electrode surface.As the concentration of heavy metal ions increased, they adsorbed onto the electrode surface and formed a layer that inhibits electron transfer between the electrode and the solution. 112Nevertheless, the response patterns for the simultaneous detection of Cd 2+ , Pb 2+ , and Cu 2+ could be easily discriminated with their response patterns and observed at the same detection potentials that appear as observed in Fig. 7, indicating that the potential separation was large enough to distinguish between the peaks.The limit of detections (LODs) of theses electrochemical sensors estimated based on a signalto-noise ratio are summarized in Table 3 and were found to be comparable with electrochemical platforms for the detection of Cd 2+ , Pb 2+ , and Cu 2+ in aqueous solutions (Table S3 †).

Fig. 2
Fig. 2 ORTEP (50% probability level) of the molecular structure of 7 with the atom numbering scheme.Hydrogen atoms are omitted for clarity.

Fig. 3
Fig. 3 ORTEP (50% probability level) of the molecular structure of 9 with the atom numbering scheme.Hydrogen atoms are omitted for clarity.The two crystallographically different molecules of 9 are denoted as A (including Fe1) and B (including Fe2).

Table 3
Linear regression equation, corresponding to the linear range, linear correlation coefficient, and LoD of the present sensing platform for Cd 2+ CN) 6 ] 3−/4− increased, and the peak-to-peak separation (DE p = 130 mV for 3, 170 mV for 6, 190 mV for 7, 170 mV for 9)